ACTH (Adrenocorticotropic Hormone)
ACTH, short for adrenocorticotropic hormone, is the pituitary signal that tells the adrenal glands to make cortisol. It sits at the center of the body's stress and steroid system and follows a strong daily rhythm.
What ACTH is
ACTH is a peptide hormone — a chain of amino acids — that the pituitary gland cuts from a much larger precursor protein called proopiomelanocortin (POMC). The same precursor also gives rise to several other small signaling fragments, which is one reason the systems controlling stress, pigmentation, and appetite can overlap. ACTH's defining job is to stimulate the adrenal glands to produce cortisol, the body's main stress steroid, along with smaller amounts of certain other adrenal steroids.
Because it controls cortisol output, ACTH influences how the body manages energy and blood sugar, responds to stress, regulates blood pressure, and dampens inflammation. It is best thought of as a relay in a chain of command rather than as a hormone that acts on the body directly: ACTH speaks almost exclusively to the adrenal cortex, and the adrenal cortex then speaks to the rest of the body through cortisol.
Where it is produced
ACTH is made by specialized cells, called corticotrophs, in the anterior (front) lobe of the pituitary gland, a structure about the size of a pea at the base of the brain. The pituitary does not act alone: it takes its instructions from the hypothalamus just above it, which sends releasing signals down a short, dedicated network of blood vessels.
What it does across body systems
- Drives cortisol: ACTH binds receptors on the adrenal cortex and prompts it to make and release cortisol, which then acts throughout the body.
- Supports adrenal structure: Steady, ongoing ACTH helps maintain the size and working capacity of the adrenal cortex; without it, the cortex tends to shrink over time.
- Other adrenal steroids: It also contributes to the production of some adrenal androgens, weak male-type hormones made by both sexes.
- Daily and stress responses: ACTH rises and falls on a predictable daily schedule and surges quickly during physical or emotional stress, illness, or low blood sugar.
How levels are regulated
ACTH is the middle link of the hypothalamic-pituitary-adrenal (HPA) axis, the body's central stress-control circuit. The hypothalamus releases corticotropin-releasing hormone (CRH), which prompts the pituitary corticotrophs to release ACTH, which in turn stimulates the adrenal cortex to release cortisol. This three-step relay lets the brain set the tone of the whole stress response from the top.
The system is kept in check by negative feedback. As cortisol rises, it travels back to the brain and pituitary and suppresses the release of both CRH and ACTH, easing off the signal so the system does not overshoot. When cortisol falls, that brake is released and ACTH climbs again. This loop is the same principle a clinician relies on during suppression and stimulation testing, where a known dose is used to see whether the axis responds as expected.
The daily rhythm
Layered on top of feedback is a strong circadian rhythm. ACTH is generally highest in the early morning, around the time of waking, and lowest in the late evening and first hours of sleep — a pattern that the cortisol rhythm closely mirrors because cortisol is its downstream product. Disruption of sleep, shift work, acute illness, and stress can all shift this rhythm, which is why the time of day a sample is taken matters so much. For more on the downstream hormone and related signals, see the hormones index.
The stress response in action
On top of its daily schedule, the HPA axis can mount a rapid response when the body faces a challenge such as injury, illness, surgery, low blood sugar, or strong emotion. The hypothalamus increases CRH, the pituitary releases a surge of ACTH, and within minutes the adrenal cortex steps up cortisol output to help mobilize energy, maintain blood pressure, and temper inflammation. Once the challenge passes, the same negative-feedback brakes bring the system back down. This combination of a steady daily rhythm with an on-demand surge is what allows a single axis to handle both routine timekeeping and emergencies. It also means that the stress of the blood draw itself, or an illness on the day of testing, can raise ACTH and complicate interpretation — another reason results are judged by a clinician who knows the full picture.
What high or low levels can be associated with
Because ACTH and cortisol form a feedback pair, their relationship to each other is usually more informative than either value alone. High ACTH can be associated with the adrenal glands being driven hard — for example when cortisol is low and the pituitary is pushing to compensate, or when a pituitary source produces excess ACTH that in turn raises cortisol. Pairing the two helps a clinician separate a problem in the pituitary from one in the adrenal glands themselves.
Low ACTH can be associated with reduced pituitary signaling, which may leave the adrenal cortex under-stimulated. Prolonged use of certain steroid medications can also lower the body's own ACTH by acting like cortisol on the feedback loop. These associations are qualitative and read only in full clinical context; see the conditions index and discuss concerns with a clinician.
How it is measured
ACTH is measured from a blood sample, usually drawn in the early morning to match the peak of its rhythm, and frequently alongside a cortisol measurement taken at the same moment. The sample often needs careful handling — chilling and prompt processing — because ACTH is fragile and breaks down quickly in a warm tube. It may form part of stimulation or suppression testing ordered by a clinician to probe how the HPA axis behaves. See the blood tests overview and the glossary for related terms.
| Timing | General pattern |
|---|---|
| Early morning | Typically highest (illustrative; varies by laboratory) |
| Midday | Falling from the morning peak (illustrative) |
| Evening | Lower (illustrative) |
| Late night | Generally lowest (illustrative; varies by laboratory, age, and method) |
Relationships with other hormones
ACTH sits between CRH above it and cortisol below it, and its meaning is best read in that chain. It also shares its parent protein, POMC, with other small signaling fragments, which links the stress system loosely to pathways involved in pigmentation and appetite. Because cortisol shapes blood sugar, blood pressure, and the immune response, the ACTH–cortisol axis interacts with the hormones that govern those systems too. To explore the neighboring messengers, see the hormones index and the glossary.
Frequently asked questions
What is the difference between ACTH and cortisol?
ACTH is the pituitary signal; cortisol is the adrenal hormone that ACTH triggers. ACTH is upstream of cortisol.
Why is ACTH usually drawn in the morning?
ACTH follows a daily rhythm that peaks early in the day, so morning draws give a more standard reference point.
Why are ACTH and cortisol tested together?
The two move in relation to each other, so seeing both helps a clinician tell whether a problem sits in the pituitary or the adrenal glands.
Where is ACTH made?
In the front part of the pituitary gland at the base of the brain, by cells called corticotrophs.
What is the HPA axis?
It is the hypothalamic-pituitary-adrenal axis: the hypothalamus signals the pituitary to release ACTH, which signals the adrenal glands to release cortisol, with feedback keeping it balanced.
Why does the ACTH sample need special handling?
ACTH is a fragile peptide that degrades quickly, so samples are often kept cold and processed promptly to keep the result accurate.
Sources
- MedlinePlus. Cortisol Test. https://medlineplus.gov/lab-tests/cortisol-test/
- MedlinePlus. Endocrine Diseases. https://medlineplus.gov/endocrinediseases.html
- Hormone Health Network. https://www.hormone.org/